Sepsis is a systemic inflammatory response syndrome (systemic inflammatory response syndrome, SIRS) caused by infection, the number of patients in the globe every year reached up to 19,000,000. Although current antibiotics and critical medical technology had been made significant development, sepsis is still a major factor of the death of infected patients, and there is no ideal treatment so far.
Research shows that the mechanism of sepsis is that the pathogen-associated molecular pattern (PAMP) released by pathogens such as bacteria, virus, fungus etc. is identified by a pattern recognition receptor (PRR) of host natural immune system, then activated the inflammatory cells, thereby triggering systemic excessive inflammatory response. Epidemiology survey shows that the PAMP that triggers sepsis mainly include lipopolysaccharide (LPS), bacterial genomic DNA (CpG DNA), peptidoglycan (PGN), lipoteichoic acid (LTA), virus RNA and zymosan. Research of American scholar Diptesh Sil et al shows a synthetic polyamines named DS-96 has antagonistic effect on LPS (Sil D, Shrestha A, Kimbrell M R, Nguyen T B, Adisechan A K, Balakrishna R, Abbo B G, Malladi S, Miller K A, Short S, Cromer J R, Arora S, Datta A, David S A. Bound to shock: protection from lethal endotoxemic shock by a novel, nontoxic, alkylpolyamine lipopolysaccharide sequestrant. Antimicrobial agents and chemotherapy. 2007; 51(8): 2811-2819.). Tony Velkov et al report polymyxin antibiotics having vast free amino groups has activity to directly antagonize LPS (Velkov T, Thompson P E, Nation R L, Li J. Structure-activity relationships of polymyxin antibiotics. Journal of medicinal chemistry. 2010; 53(5): 1898-1916.). Chinese invention patent CN102267922B disclosed a polyamine compounds having good antagonistic effect on LPS and CpG DNA.
As previously mentioned, the PAMP as pathogenic factor that triggers sepsis has numerous sources and varieties, but all of drugs so far discovered only antagonize one or several PAMP, it may be difficult to cure sepsis comprehensively and effectively. So it is of important significance to find a drug that can antagonize more PAMP at the same time.